Gene therapies for neurodegenerative disorders targeting ganglioside biosynthetic pathways

Abstract

A composition of matter comprising an adeno-associated virus (AAV) or other human compatible virus, encoding the gene for Sialidase Neu3, B3Galt4, St3Gal2, or combinations thereof, and a neuron specific promoter, wherein the composition is suitable for administration to a patient comprising injecting the AAV or other human compatible virus into the brain by intracranial stereotaxic injunction; wherein the AAV's encoding for the Sialidase Neu3, B3Galt4, St3Gal2, or combinations thereof enhance and/or normalize levels of GM1 in neurons, providing both therapeutic relief and disease modifying effects in specific areas of the brain relevant to particular neurodegenerative diseases.

1 .- 33 . (canceled) 
     
     
         34 . A method of treating neurodegenerative disease in a subject in need thereof, the method comprising administering to said subject an effective amount of a vector encoding sialidase Neu3; wherein said vector modifies cells in said subject to increase production of Neu3, thereby increasing the amount of GM1 in the brain of said subject. 
     
     
         35 . The method of  claim 34 , further comprising administering to said subject a vector encoding B3Galt4. 
     
     
         36 . The method of  claim 34 , further comprising administering to said subject a vector encoding B3Galt4, St3Gal2, or combinations thereof. 
     
     
         37 . The method of  claim 36  wherein said vector encoding sialidase Neu3 and/or said vector encoding B3Galt4, St3Gal2, or combinations thereof is a viral vector selected from the group consisting of retrovirus, lentivirus, adenovirus, and adeno-associated virus (AAV) vector. 
     
     
         38 . The method of  claim 36  wherein said vector encoding sialidase Neu3 and/or the vector encoding B3Galt4, St3Gal2, or combinations thereof is a non-viral vector. 
     
     
         39 . The method of  claim 34 , further comprising concomitantly administering to said subject a dietary supplement with complex milk lipids (CMLs) having a concentrated dietary source of GM3. 
     
     
         40 . The method of  claim 34 , further comprising concomitantly administering shRNA/siRNA St3gal2 to increase GM1 levels. 
     
     
         41 . The method of  claim 34 , wherein the neurodegenerative disease is Parkinson's disease or Huntington's disease.